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挖掘新兴骨肉瘤治疗中免疫学方法的复杂性:一项结合最新临床试验的综合叙述性综述

英文原题:Digging Through the Complexities of Immunological Approaches in Emerging Osteosarcoma Therapeutics: A Comprehensive Narrative Review with Updated Clinical Trials.

PubMed 2025/03/08(内容时间) Biomedicines Q2 · IF 4.5(JCR 2025)

研究概要

手术与新辅助化疗及术后化疗的结合,已使局限性OS肿瘤患者的5年生存率显著提高至70%以上。

中文摘要

骨肉瘤(OS)是肿瘤学和病理学中最主要的间叶性原发性恶性骨肿瘤,影响从青少年到老年人的广泛年龄范围。它常进展为肺转移,最终导致OS患者死亡。由于其异质性,导致OS进展和播散的确切病理途径尚未完全阐明。手术联合新辅助和术后化疗已使局限性OS肿瘤患者的5年生存率显著提高至70%以上。然而,约30%的患者出现局部复发和/或转移。因此,需要创新的治疗方法来解决传统治疗的局限性。免疫治疗作为对标准化疗耐药的肿瘤(包括OS)的一种有前景的途径,已获得越来越多的关注,尽管疾病进展和播散的潜在机制仍未完全阐明。由于肿瘤的免疫抑制微环境和有限的免疫原性,免疫治疗可能不适合用于OS患者。然而,目前有一些基于免疫的治疗正在开发用于临床,如双特异性抗体、CAR-T 细胞和免疫检查点抑制剂。此外,其他免疫治疗技术包括细胞因子、疫苗和修饰的自然杀伤(NK)细胞/巨噬细胞正处于早期研究阶段,但在不久的将来肯定会成为热门课题。我们撰写这篇综述的目的是通过总结检查不同方法的临床前和当前临床研究的结果,激发对OS免疫治疗的新研究方向。

展开英文摘要原文

Osteosarcoma (OS) is the predominant mesenchymal primary malignant bone tumor in oncology and pathology, impacting a wide age range from adolescents to older adults. It frequently advances to lung metastasis, ultimately resulting in the mortality of OS patients. The precise pathological pathways responsible for OS progression and dissemination are not fully understood due to its heterogeneity. The integration of surgery with neoadjuvant and postoperative chemotherapy has significantly increased the 5-year survival rate to more than 70% for patients with localized OS tumors. However, about 30% of patients experience local recurrence and/or metastasis. Hence, there is a requirement for innovative therapeutic approaches to address the limitations of traditional treatments. Immunotherapy has garnered increasing attention as a promising avenue for tumors resistant to standard therapies, including OS, despite the underlying mechanisms of disease progression and dissemination remaining not well elucidated. Immunotherapy may not have been suitable for use in patients with OS because of the tumor's immunosuppressive microenvironment and limited immunogenicity. Nevertheless, there are immune-based treatments now being developed for clinical use, such as bispecific antibodies, chimeric antigen receptor T cells, and immune checkpoint inhibitors. Also, additional immunotherapy techniques including cytokines, vaccines, and modified-Natural Killer (NK) cells/macrophages are in the early phases of research but will certainly be popular subjects in the nearest future. Our goal in writing this review was to spark new lines of inquiry into OS immunotherapy by summarizing the findings from both preclinical and current clinical studies examining different approaches.

论文信息

作者
Sergi CM、Burnett M、Jantuan E、Hakoum M、Beug ST、Leng R、Shen F
第一作者单位
Division of Anatomic Pathology, Department of Laboratory Medicine, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON K1H 8L1, Canada.Canada
通讯作者单位
Department of Laboratory Medicine, Stollery Children's Hospital, University of Alberta, Edmonton, AB T6G 2R3, Canada.Canada
文献类型
综述
期刊
Biomedicines2025 Mar 8
原文标识
PubMed 40149640 · DOI 10.3390/biomedicines13030664